AIM:The objective of this study is to examine the expression of profilin 1(PFN1)in mice with di-abetic nephropathy and determine its association with immune cell infiltration.METHODS:This study presents an analy-sis of PFN1 expression and immune cell infiltration in patients with diabetic nephropathy,utilizing transcriptome expres-sion data from kidney tissue microarray.Additionally,the findings were validated in a diabetic nephropathy mouse model.Sixteen C57BL/6 mice were randomly assigned into two groups,namely the normal group and the model group,in an equal manner.The model group underwent the establishment of the diabetic nephropathy model through intraperitoneal injection of streptozotocin.Subsequently,the expression levels of CD11b,F4/80,CC chemokine receptor 4(CCR4),interleukin-1 receptor type I(IL-1R1),B-cell lymphoma-2(Bcl-2),Bcl-2-associated X protein(Bax)and caspase-3 in kidney tissue were assessed upon successful establishment of the diabetic nephropathy model.Furthermore,the overexpression of PFN1 was observed in a cellular model of diabetic nephropathy,and the protein expression levels of monocyte chemotactic pro-tein-1(MCP-1)and caspase-3 were assessed.RESULTS:The expression of PFN1 was found to be significantly in-creased in the GSE30122 dataset of transcriptome expression in kidney tissues affected by diabetic nephropathy(P＜0.01).This increase in PFN1 expression was found to be correlated with the presence of macrophages and T cells.Fur-thermore,the renal tissue of the diabetic nephropathy model group exhibited significant pathological changes.In this mod-el group,the expression levels of PFN1,CD11b,F4/80,CCR4,IL-1R1,Bax,Bcl-2,and caspase-3 were all significant-ly increased(P＜0.01).Overexpression of PFN1 could enhance the expression of MCP-1 and caspase-3 proteins.CON-CLUSION:Macrophages and Th17 cells were identified within the renal tissue of mice with diabetic nephropathy,con-comitant with an up-regulation in the expression of PFN1.This up-regulation was observed to facilitate the induction of apoptosis in the context of diabetic nephropathy.

Chronic mountain sickness (CMS) or Monge syndrome is a disease that is prevalent at altitude above 2 500 meters. High altitude polycythemia (HAPC) is one subtype of CMS. EPAS1 and EGNL1 are the most critical high-altitude adaptation genes in the genome of the Tibetan population. The HIF-PHD-VHL system plays an important role in the pathogenesis of HAPC. The protease encoded by the SENP1 gene regulates hypoxia related transcription factors such as HIF and GATA to affect the expression of EPO or EPOR involved in red blood cell generation. With the development of genetic testing and omics technology, new progress in the fields of metabolomics, proteomics and metabolomics has been made in the pathogenesis of HAPC. The above new research results provide a preliminary basis for bone marrow hematoecology and hematopoietic regulation of HAPC. The diagnostic criteria for CMS have certain limitations, especially in patients with excessive erythrocytosis who should undergo genetic testing recommended for congenital and polycythemia vera. This article provides a review of the latest research on HAPC in various omics techniques, hematopoietic regulation and diagnostic processes which is more conducive to understand the pathogenesis. The clinical diagnosis of excessive erythrocytosis emphasizes the importance of genetic testing.

Objective:To explore the relevancy between the uridine diphosphate-glucuronylgly-cosyltransferase 1A1 (UGT1A1) gene mutation and the phenotype of indirect hyperbilirubinemia in children.Methods:Sixteen cases with indirect hyperbilirubinemia who visited the Department of Gastroenterology, Children's Hospital of Nanjing Medical University from July 2013 to November 2019 were retrospectively analyzed and were divided into Gilbert syndrome (GS), Crigler-Najjar syndrome type II (CNS-II), and indirect hyperbilirubinemia groups unexplained by UGT1A1 gene mutations. The differences in gene mutation site information and general clinical data were compared. The association between gene mutation spectrum and bilirubin level was explored by t-test analysis.Results:Ten of the sixteen cases with indirect hyperbilirubinemia had GS, three had CNS-II, and three had indirect hyperbilirubinemia unexplained by UGT1A1 gene mutations. A total of six mutation types were detected, of which c.211G?>?A accounted for 37.5% (6/16), c.1456T?>?G accounted for 62.5% (10/16), and TATA accounted for 37.5% (6/16), respectively. Compared with the GS group, the CNS group had early disease onset incidence, high serum total bilirubin ( t ?=?5.539, P ??0.05) and age of onset ( t ?=?0.3611, P ?>?0.05) between the two groups. There was no significant correlation between the number of UGT1A1 gene mutations and serum bilirubin levels. Children with c.1456T?>?G homozygous mutations had the highest serum bilirubin levels. Conclusion:The common pathogenic variants of the UGT1A1 gene sequence are c.1456T?>?G, c.211G?>?A, and TATA, indicating that these site mutations are related to the occurrence of indirect hyperbilirubinemia and have important guiding significance for the etiological analysis of indirect hyperbilirubinemia in children.

Purpose/Significance To analyze the dynamic changes,influencing factors and weak links of e-health literacy of middle-aged and elderly people,so as to provide references for improving e-health literacy of middle-aged and elderly people.Method/Process A questionnaire survey is conducted among 505 middle-aged and elderly people in Guangzhou,and the results are analyzed by using SPSS 24.0.Result/Conclusion The average score of e-health literacy of middle-aged and elderly people is in the middle level;The weak link of e-health literacy is the lack of health information interaction and evaluation capacity.Individual factors are the primary factors that affect e-health literacy of middle-aged and elderly people.It is suggested to increase policy and financial support,carry out"the younger population helps the aging population"mode,and elderly-oriented transformation of digital health Apps.

Objective:To assess the treatment outcomes of endoscopic ultrasound-guided biliary drainage (EUS-BD) in patients with obstructive jaundice due to unsuccessful endoscopic retrograde cholangiopancreatography (ERCP).Methods:The clinical data of patients with obstructive jaundice who underwent EUS-BD due to ERCP failure at the Gastrointestinal Endoscopy Center of Beijing Friendship Hospital from September 2018 to November 2023, was retrospectively collected and analyzed. We explored the technical success, clinical success, and adverse events associated with EUS-BD.Results:In total, 43 EUS-BD procedures were performed in 39 patients with a technical success rate of 86.0% (37/43). The clinical success rate was 81.1% (30/37). Biliary drainage was not effectively achieved in seven cases, including two fatal cases and five cases of recurrent postoperative biliary obstruction. The incidence of adverse events was 21.6% (8/37), including two cases of postoperative bile leakage peritonitis, two cases of stent displacement, one case of stent dislocation, one case of perforation, and two cases of death.Conclusion:EUS-BD is a relatively safe and effective method for bile duct drainage, serving as a dependable alternative therapeutic option for patients with obstructive jaundice due to unsuccessful ERCP.

Objective:To compare the efficacy of domestic and imported hemostatic clips in preventing delayed post-polypectomy bleeding (DPPB) after endoscopic resection of colorectal polyps ≥ 10 mm.Methods:Clinical data of 789 patients who underwent endoscopic resection of colorectal polyps (polyp diameter ≥10 mm) in Beijing Friendship Hospital, Capital Medical University from January 2018 to December 2019 were collected. The patients were divided into DPPB group ( n=15) and non-DPPB group ( n=774). Univariate and multivariate logistic regression models were used to analyze the influential factors for DPPB. The patients using one type of hemostatic clip were divided into the domestic hemostatic clip group ( n=499) and the imported hemostatic clip group ( n=208). The efficacy of hemostatic clips in preventing DPPB in the two groups was compared. Results:Among the 789 patients undergoing endoscopic resection of colorectal polyps, 1.9% (15/789) suffered from DPPB. Multivariate logistic regression analysis showed that pedunculated polyp was an independent risk factor for DPPB ( OR=6.621, 95% CI: 2.278-19.241, P=0.001), and closure of mucosal defect was an independent protective factor for DPPB ( OR=0.169,95% CI: 0.050-0.570, P=0.004). Regardless of physician experience, there was no significant difference between the domestic and imported hemostatic clip group in preventing DPPB after endoscopic resection of colorectal polyps ≥10 mm [experienced physicians: 1.8% (7/385) VS 0.6% (1/175), χ2=1.314, P=0.445; common physicians: 2.6% (3/114) VS 3.0% (1/33), χ2=0.010, P>0.999]. The domestic hemostatic clip group paid for less medical expenses than the imported hemostatic clip group (experienced physicians: 1 433.51±889.02 yuan VS 3 033.97±1 686.87 yuan, t<0.001 , P<0.001; common physicians: 1 181.58±815.29 yuan VS 3 303.46±1 690.43 yuan, t<0.001 ,P<0.001). Conclusion:Pedunculated polyp is an independent risk factor for DPPB after endoscopic resection of colorectal polyp larger than 10 mm, and clipping can significantly reduce the risk for DPPB. There is no significant difference in the prevention of DPPB between domestic and imported clips, but domestic clips compared with imported clips yield less medical burden, which are suitable for promotion to primary hospitals and major clinical centers.

OBJECTIVE: To explore the clinical features and genetic basis of a patient with glycogen storage disease type VI (GSD-VI). METHODS: Clinical data of the patient was collected. Genomic DNA was extracted from peripheral blood samples of the proband and his parents. Genetic variants were detected by using whole exome sequencing. Candidate variants were verified by Sanger sequencing followed by bioinformatics analysis. RESULTS: The proband presented fasting hypoglycemia, hepatomegaly, growth retardation, transaminitis, metabolic acidosis and hyperlactatemia. Liver biopsy indicated GSD. Novel compound heterozygous PYGL gene variants (c.2089A>G/c.158_160delACT) were detected in the proband. Compound heterozygosity was confirmed by Sanger sequencing of the patient's genomic DNA. Provean and MutationTaster predicted the two variants as deleterious and the variant sites are highly conserved. CONCLUSION The compound heterozygous variants (c.2089A>G/c.158_160delACT) of PYGL gene probably underlay the GSD in the patient. The two novel variants have expanded the spectrum of PYGL gene variants and provided the basis for genetic counseling of the family.
Child ; Family ; Genetic Testing ; Glycogen Storage Disease Type VI/genetics* ; Humans ; Mutation ; Whole Exome Sequencing

Objective:To analyze the risk factors for the most common adverse events, i.e. abdominal pain and distension in sedation-free colonoscopy.Methods:This was a multicenter clinical study, in which clinical data of patients including outpatients and inpatients who underwent selective sedation-free colonoscopy at six gastrointestinal endoscopy centers from July 2017 to December 2019 were collected, including patients' general information, complicating diseases, examination time, examination results, and occurrence of adverse events of abdominal pain and distension. Univariate and multivariate logistic regression was performed to analyze the risk factors for adverse events of abdominal pain and distension during sedation-free colonoscopy.Results:A total of 2 394 patients underwent sedation-free colonoscopy, among whom 690 (28.8%) suffered from abdominal pain, and 1 151 (48.1%) experienced abdominal distension. The results of multivariate logistic analysis showed that overweight ( OR=1.33, 95% CI:1.09-1.62, P=0.005), obesity ( OR=1.55, 95% CI:1.14-2.11, P=0.005) and combination of hypertension ( OR=1.58, 95% CI:1.23-2.02, P<0.001) were independent risk factors for abdominal pain during sedation-free colonoscopy, and overweight ( OR=1.40, 95% CI:1.17-1.68, P<0.001) and combination of hypertension ( OR=1.39,95% CI:1.10-1.76, P=0.006) were independent risk factors for abdominal distension during sedation-free colonoscopy. Conclusion:Obesity, overweight and combination of hypertension are independent risk factors for abdominal pain, and overweight and combination of hypertension are independent risk factors for abdominal distension during sedation-free colonoscopy.

Objective:To explore the relationship between soft markers found in the first trimester (11-13 + 6 gestational weeks) ultrasound screening and fetal adverse pregnancy outcomes. Methods:Single pregnancy fetuses were selected from the Multicenter Clinical Study of First Trimester Screening in China during August 2017 to August 2020. The types and detection rate of soft markers during the first trimester were compared. The correlation between positive soft markers and adverse pregnancy outcomes was analyzed by binary Logistics regression.Results:A total of 16 625 fetuses with complete follow-up outcomes were included in the group. Six hundred and seven ultrasonic soft markers were detected in 556 fetuses with positive soft markers during the first trimester, and the first four most frequently occurred were increased nuchal translucency (NT) (2.08%, 345/16 625), echogenic intracardiac focus (EIF) (0.94%, 156/16 625), hypoplasia of fetal nasal bone (0.20%, 34/16 625), single umbilical artery (SUA) (0.19%, 31/16 625). Among 556 fetuses, the incidence of adverse pregnancy outcome in fetuses with two or more positive soft markers was 32.50% (13/40), which was significantly higher than fetuses with single positive soft marker (11.05%, 57/516), and the difference was statistically significant (χ 2=5.055, P<0.001). The incidence of adverse pregnancy outcome in positive soft markers fetus associated with structural abnormalities was 80.77% (21/26), which was significantly higher than fetuses with isolated positive soft marker (12.08%, 64/530), and the difference was statistically significant (χ 2=90.310, P<0.001). Binary logistic regression analysis showed choroid plexus cyst (CPC), SUA, echogenic bowel (EB), absent/reversed a-wave of ductus venosus, hypoplasia of fetal nasal bone, increased NT, and EIF were closely related to the adverse pregnancy outcomes (all P<0.05). However, there were no significant correlations between tricuspid regurgitation (TR), pyelectasis (PYE) and fetal adverse pregnancy outcomes (all P>0.05). Conclusions:The ultrasonic soft markers during the first trimester are of great significance in predicting fetal adverse pregnancy outcomes. For multiple positive soft markers or positive soft markers combined with structural abnormalities, more attention should be paid to them and comprehensive evaluation is required to be carried out.

A 2-year- and 2-month-old girl developed recurrent eczema-like rashes 7 days after birth, followed by the occurrence of poikiloderma and hair loss. Cholestasis occurred at the age of 1 month and 10 days, which was improved but serum transaminase levels were elevated after 4 months. The patient usually presented with slight sweating, heat intolerance, and delayed gross motor development. Skin examination showed generalized mottled hypo- and hyper-pigmented patches, especially in the exposed areas, and sparse hair and eyebrows. Her parents had no similar clinical manifestations. Whole-exome sequencing showed a mutation c.1883G>A (p.Ser628Asn) in the FAM111B gene in the child, which was not found in her parents. According to the typical skin lesions, abnormal liver function and genetic testing results, this patient was diagnosed with hereditary fibrosing poikiloderma with tendon contracture, myopathy, and pulmonary fibrosis, and the mutation c.1883G>A in the FAM111B gene may be the cause of the patient′s clinical manifestations. The patient received hepatoprotective therapy, sun screen intervention, rehabilitation training, etc. After 10-month follow-up, the patient still presented with skin lesions and elevated transaminases, but without other discomforts.